Primary chemoradiotherapy (CRT) is a well-established treatment for locally advanced head and neck squamous cell carcinoma (HNSCC). However, not every patient has a complete response to this treatment modality, necessitating eventual salvage neck dissection. Some patients with persistent adenopathy following chemoradiotherapy (CRT) for HNSCC may harbour viable disease. Improved selection is needed to prevent unnecessary salvage neck dissection. In this study diagnostic accuracy of ultrasonography-guided FNA results was compared with the standard of surgical pathologic examination of neck dissection specimens. Ultrasonography-guided FNA was performed on 17 lymph nodes. It identified squamous cell carcinoma in the aspirates of four (80%) of the five nodes with squamous cell carcinoma identified on pathologic testing and confirmed the absence of disease in the remaining 12 (71%) lymph nodes. The statistical analysis of these results revealed: a sensitivity of 80%; specificity of 100%; a positive predictive value of 100% and a negative predictive value of 92.3%. The diagnostic accuracy of ultrasonography-guided FNA at detecting residual persistent cancer was 88%. This pilot study suggests that ultrasonography-guided FNA may be a feasible ancillary diagnostic imaging tool to imaging to assess patients with radiographic persistent disease prior to consideration of salvage neck dissection.